99mTc-3Cboroxime: a novel 99mTc(iii) complex [99mTcCl(CDO)(CDOH)2B-3C] (CDOH2 = cyclohexanedione dioxime; 3C-B(OH)2 = 3-(carbamoylphenyl)boronic acid) with high heart uptake and long myocardial retention

Dalton Transactions Pub Date: 2017-05-31 DOI: 10.1039/C7DT01292F

Abstract

In this study, a new 99mTc(III) complex [99mTcCl(CDO)(CDOH)2B-3C] (99mTc-3Cboroxime: CDOH2 = cyclohexanedione dioxime; 3C-B(OH)2 = 3-(carbamoylphenyl)boronic acid) was evaluated as a radiotracer for heart imaging. 99mTc-3Cboroxime was prepared in high radiochemical purity (RCP > 95%). Biodistribution and imaging studies were performed using Sprague–Dawley rats (200–225 g). We found that the heart uptake of 99mTc-3Cboroxime (3.43 ± 0.11%ID g?1) at 2 min postinjection (p.i.) was close to that of 99mTc-Teboroxime (3.00 ± 0.37%ID g?1), and the heart uptake value of 99mTc-3Cboroxime was almost unchanged over the first 15 min (3.05 ± 0.35%ID g?1 at 15 min p.i.). 99mTc-3Cboroxime had lower uptake than 99mTc-Teboroxime in the blood, lungs and muscle over a 60 min period. Its heart/blood, heart/lung and heart/muscle ratios were better than those of 99mTc-Teboroxime. These results suggest that 99mTc-3Cboroxime has a significant advantage over 99mTc-Teboroxime with respect to myocardial retention and heart/background ratios. However, its liver uptake at 2 min p.i. was higher than that of 99mTc-Teboroxime. Because of its faster liver clearance, 99mTc-3Cboroxime had heart/liver ratios close to or better than that of 99mTc-Teboroxime at ≥5 min p.i. As a result, good quality SPECT images could be obtained in any of the 5 min imaging windows over the first 20 min after injection of 99mTc-3Cboroxime. More importantly, the results from this study show that the use of the 3-carbamylphenyl group is an interesting approach to achieve long heart retention for new 99mTc(III) radiotracers. Future research will focus on further minimizing liver radioactivity while maintaining high heart uptake over a wide time window.

Graphical abstract: 99mTc-3Cboroxime: a novel 99mTc(iii) complex [99mTcCl(CDO)(CDOH)2B-3C] (CDOH2 = cyclohexanedione dioxime; 3C-B(OH)2 = 3-(carbamoylphenyl)boronic acid) with high heart uptake and long myocardial retention
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